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Hepatocellular carcinoma (HCC), a major form of liver cancer, is characterized by high lethality and a multifactorial etiology that includes hepatitis virus infections, lifestyle factors, and genetic predispositions. This study aimed to explore the impact of ZNF208 gene polymorphisms on the clinicopathological features of Taiwanese HCC patients, focusing on three specific single nucleotide polymorphisms (SNPs): rs2188971, rs2188972, and rs8105767. Our cohort consisted of 438 HCC patients and 1193 control individuals. Clinical staging was determined using the tumor/node/metastasis (TNM) system, and various clinical indicators were collected. Our analysis revealed a statistically significant increase in ZNF208 expression in HCC patients compared to controls, indicating a potential role in HCC progression. Although no substantial association was observed between ZNF208 SNPs and increased HCC risk, specific clinical features such as distant metastasis and vascular invasion showed significant associations with these SNPs, suggesting their influence on disease aggressiveness. Demographic analyses highlighted the importance of factors like alcohol consumption and viral hepatitis markers in HCC. Our study underscores the complexity of genetic influences on HCC, with ZNF208 polymorphisms potentially affecting tumor progression and patient outcomes.
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Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. One single-nucleotide (rs55829688) and one insertion/deletion polymorphism (rs145204276) of GAS5 gene were surveyed in 778 DKD cases and 788 DKD-free diabetic controls. We demonstrated that diabetic subjects who are heterozygous at rs55829688 (TC; AOR, 1.737; 95% CI, 1.028-2.937; p=0.039) are more susceptible to advanced DKD but not early-staged DKD, as compared to diabetic subjects who are homozygous for the major allele of rs55829688 (TT). Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD.
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Nefropatías Diabéticas , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios de Casos y Controles , Alelos , Adulto , Estudios de Asociación GenéticaRESUMEN
OBJECTIVE: One-third of head and neck squamous cell carcinomas are early-stage oral cavity squamous cell carcinomas (OCSCC). Despite a high curative rate, 20% of early-stage OCSCC patients do not achieve long-term survival. This study evaluates the role of adjuvant therapy (ADJ) in delaying disease progression and prolonging survival. METHODS: This single-institute retrospective cohort study enrolled 481 early-stage OCSCC patients, 16% (78/481) of whom received ADJ. It was reported according to the STROBE guidelines. Cox proportional hazards regression and Kaplan-Meier survival curves were employed to identify suitable candidates for ADJ. RESULTS: The 5-year locoregional recurrence-free survival (LR-RFS) and overall survival rates were 73.2% and 84.9%, respectively. Positive margins and advanced depth of invasion (DOI) were independent predictors of LR-RFS. For patients with positive margins, adjuvant chemoradiotherapy (CRT) was superior to adjuvant radiotherapy alone in improving LR-RFS (hazard ratios for adjuvant CRT vs. none, 0.042; adjuvant radiotherapy alone vs. none, 0.702). Excluding positive margins, advanced DOI was the most critical factor in assessing the need for ADJ. Positive margins and advanced DOI were more appropriate criteria than EORTC 22931/RTOG 9501 for evaluating adjuvant CRT. CONCLUSIONS: Adjuvant CRT was indicated for patients with positive margins and advanced DOI to improve survival outcomes.
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OBJECTIVE: Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism. METHODS: Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors. RESULTS: In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells. CONCLUSIONS: Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.
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The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events.
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To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002-1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population.
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Glucemia , Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Masculino , Anciano , Femenino , Fracturas por Compresión/cirugía , Fracturas por Compresión/mortalidad , Fracturas Osteoporóticas/cirugía , Fracturas Osteoporóticas/mortalidad , Fracturas de la Columna Vertebral/mortalidad , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/etiología , Glucemia/análisis , Glucemia/metabolismo , Estudios Retrospectivos , Anciano de 80 o más Años , Periodo Preoperatorio , Factores de Riesgo , Modelos de Riesgos Proporcionales , Hiperglucemia/mortalidad , Hiperglucemia/complicaciones , Hiperglucemia/etiologíaRESUMEN
We aim to explore the possible association between ovarian cancer and the subsequent development of open-angle glaucoma (OAG) using the Taiwan Longitudinal Health Insurance Database (LHID) 2000. A retrospective cohort study was executed, and individuals with ovarian cancer were enrolled and age-matched (with a 1:4 ratio) to non-ovarian cancer individuals. A total of 4990 and 19,960 patients were put into the ovarian cancer and control groups. The main outcome was the presence of OAG according to the LHID 2000 codes. The Cox proportional hazard regression was adopted to demonstrate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the ovarian cancer and control groups. There were a total of 241 and 1029 OAG cases observed in the ovarian cancer group and the control group, respectively. The incidence of OAG was significantly higher in the ovarian cancer group than in the control group according to multivariable analysis (aHR: 1.18, 95% CI: 1.02-1.37, p = 0.022). The ovarian cancer patients older than 60 years showed a significantly higher risk of OAG compared to the non-ovarian cancer individuals of the same age (aHR: 1.39, 95% CI: 1.16-1.63, p = 0.001). Additionally, ovarian cancer individuals with a disease interval of more than two years presented a significantly higher incidence of OAG than the non-ovarian cancer group (p < 0.05). In conclusion, ovarian cancer positively correlates with a high rate of subsequent OAG, especially in elderly persons with a long disease interval.
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We aim to evaluate the effectiveness of an acupuncture steam-warming eye mask (ASEM) on dry eye disease (DED) in visual display terminal (VDT) users. This prospective randomized clinical trial included VDT users with DED-related features who were randomly assigned to the ASEM group (ASEM for 2 weeks, 20 participants) or the steam-warming eye mask (SEM) group (SEM for 2 weeks, 20 participants). The tear film break-up time (TBUT), Schirmer test, tear meniscus height, ocular surface staining scores, eyelid and meibomian gland exam, subjective symptoms, and quality of life (QoL) scores before and after treatment were collected. A generalized linear mixed model was applied to compare the improvement of symptoms and signs between the two groups. After the 2-week treatment, all the subjective symptoms and questionnaire scores in the ASEM group improved significantly (all p < 0.05), whereas the feelings of relaxation, comfortable, and refreshment did not change in the SEM group (both p > 0.05). The TBUT, tear meniscus height, and meibum quality in the lower eyelid were significantly better in the ASEM group than the SEM group (all p < 0.05), whereas no significant changes were observed in the Schirmer test and ocular surface staining scores. Compared with the SEM group, the ASEM group experienced a stronger feeling of refreshment (p = 0.013), lower sensation of ocular discharge (p = 0.031), higher TBUT (p = 0.045), better meibomian gland expressibility of both eyelids (both p < 0.05), and better meibum quality of both eyelids (both p < 0.05), even after adjustments for age and sex. In conclusion, comparing with SEM, ASEM can improve some subjective DED symptoms, tear film stability, and meibum status in VDT users.
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Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern-recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer-associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single-nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity-matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically-confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age-specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa.
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Proteína C-Reactiva , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Metástasis de la Neoplasia , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata , Componente Amiloide P Sérico , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Polimorfismo de Nucleótido Simple/genética , Anciano , Persona de Mediana Edad , Alelos , Genotipo , Estudios de Casos y Controles , Línea Celular TumoralRESUMEN
Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.
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Movimiento Celular , Chalconas , Metaloproteinasa 2 de la Matriz , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Invasividad Neoplásica , Factor de Transcripción STAT3 , Transducción de Señal , Humanos , Factor de Transcripción STAT3/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Chalconas/farmacología , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Transducción de Señal/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
We aimed to survey the potential correlation between biometric parameters and postoperative outcomes after implanting extended depth-of-focus (EDOF) intraocular lenses (IOLs) and trifocal IOLs. A retrospective cohort study was conducted, and patients receiving EDOF or trifocal IOL implantations were included. In total, 36 and 26 eyes were enrolled in the EDOF and trifocal groups, respectively. The primary outcomes of this study were the postoperative uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), and spherical equivalent (SE). The generalized linear model was applied to evaluate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) of primary outcomes in patients with different biometric characters. The final UDVA of the EDOF group was significantly better than that of the trifocal group (p = 0.020), and the UNVA and SE did not show significant differences between the two groups throughout the postoperative period (all p > 0.05). In a multivariable analysis, the UDVA was significantly better in the EDOF group than in the trifocal group (p = 0.038). For the subgroup analysis, the high axial length (AXL) value correlated to a lower postoperative UDVA in the EDOF group (both p < 0.05). Additionally, a large white-to-white (WTW) diameter was related to worse postoperative UNVA in the trifocal group (p = 0.042), and a high AXL was associated with higher SE in both the EDOF and trifocal groups (both p < 0.05). In conclusion, a high AXL correlates to worse postoperative outcomes in both the EDOF and trifocal IOLs, and trifocal IOL outcomes could be affected by large WTW diameters.
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In this study, we aim to evaluate the risk factors of myopia undercorrection in recipients of second-generation keratorefractive lenticule extraction (KLEx) surgery. A retrospective case-control study was performed, and patients who received second-generation KLEx surgery were enrolled. The cases with myopia undercorrection were matched to non-myopia undercorrection cases with a 1:4 ratio according to age, and a total of 22 and 88 eyes were categorized into the undercorrection and control groups, respectively. Demographic, refractive, topographic, and surgical data were collected preoperatively. A generalized linear model was operated to evaluate the potential risk factors for myopia undercorrection. The uncorrected distance visual acuity (UDVA) at three months postoperation was significantly better in the control group (p = 0.006), and residual myopia and SE were significantly higher in the undercorrection group during the whole follow-up period (all p < 0.001). The UDVA value showed a trend of improvement in the control group (p < 0.001), and the changes to SE and residual myopia were significantly lower in the control group (both p < 0.001). Regarding the risk factors for myopia undercorrection in the whole population and the high-myopia population, a higher manifest sphere power, higher steep keratometry (K), higher topographic cylinder, lower central corneal thickness (CCT) at apex, higher CCT difference and lower residual stromal thickness (RST) correlated to myopia undercorrection (all p < 0.05). In the low-myopia population, only higher myopia and lower RST correlated to myopia undercorrection (both p < 0.05). In conclusion, a high-sphere power and irregular topographic pattern correlated to myopia undercorrection after the second KLEx surgery, especially for individuals with high myopia.
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In this study, we aimed to investigate the effect of different hyaluronic acid (HA)-containing artificial tears on dry eye disease (DED) treatment in combination with intense pulsed light (IPL) therapy. A retrospective cohort study was conducted, and the participants received IPL therapy and HA-containing artificial tears. There were 42 and 40 eyes in the 0.10% and 0.15% HA groups after selection, respectively. The main outcomes were the postoperative non-invasive tear break-up time (NITBUT), Schirmer II test results, ocular surface stain, and numbers of DED-related symptoms. A generalized linear model was utilized to produce the adjusted odds ratio (aOR) and 95% confidence interval (CI) of the main outcomes between groups. At the three-month follow-up, the NITBUT was significantly higher in the 0.15% HA group (p = 0.023), and the NITBUT recovery was also significantly better in the 0.15% HA group compared to the 0.10% HA group (p = 0.039). The multiple DED-related symptoms significantly correlated with no DED symptom improvement in both the 0.10% and 0.15% HA groups (both p < 0.05), while the low pre-treatment NITBUT was marginally related to no DED symptom improvement in the 0.10% HA group (p = 0.047). A low NITBUT and Schirmer II test result correlated with no DED symptom improvement in both the groups (all p < 0.05). In conclusion, the application of 0.10% and 0.15% HA-containing artificial tears revealed similar effects to IPL therapy for DED.
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BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance. PATIENTS AND METHODS: This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes. RESULTS: The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC. CONCLUSION: This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy.
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Biomarcadores de Tumor , Proteínas de Unión al Calcio , Carcinoma Hepatocelular , Citoplasma , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Biomarcadores de Tumor/metabolismo , Citoplasma/metabolismo , Anciano , Adulto , Estimación de Kaplan-Meier , Inmunohistoquímica , Estadificación de Neoplasias , Moléculas de Adhesión CelularRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.
High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.
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Ciclosporina , Quimioterapia Combinada , Síndromes de Ojo Seco , Humanos , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Adulto , Índice de Severidad de la Enfermedad , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversosRESUMEN
AIM: We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. RESULTS: After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. CONCLUSIONS: In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.
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Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future.
Asunto(s)
Apoptosis , Quinolinas , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Quinolinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos/farmacología , Células HeLa , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Ratones Desnudos , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Endogámicos BALB C , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Movimiento Celular/efectos de los fármacosRESUMEN
AIM: We attempted to test the influences of cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms on the susceptibility to Diabetic retinopathy (DR). METHODS: Five single-nucleotide polymorphisms (SNPs) of the CDKN2B-AS1 gene, rs564398, rs1333048, rs1537373, rs2151280, and rs8181047 were examined in 280 DR cases and 455 DR-free diabetic controls. RESULTS: Among these loci tested, we demonstrated that diabetic carriers of at least one polymorphic allele (G) of rs2151280 (AG and GG; AOR, 1.613; 95% CI, 1.040-2.501; p = 0.033) are more susceptible to proliferative DR but not non-proliferative DR. This genetic association with the risk of developing proliferative DR was further strengthened in homozygotes for the polymorphic allele (G) of rs2151280 (GG; AOR, 2.194; 95% CI, 1.117-4.308; p = 0.023). We detected a significant association of the polymorphic allele (G) of rs2151280 with proliferative DR patients (OR, 1.503; 95% CI, 1.112-2.033; p = 0.008) but not with the entire DR or non-proliferative DR group. Moreover, as compared to those who do not possess the polymorphic allele of rs2151280 (AA), DR patients carrying at least one polymorphic allele of rs2151280 (AG + GG) exhibited a lower glomerular filtration rate and HDL cholesterol level, revealing a promotive role of rs2151280 in renal and cardiovascular complications of diabetes. CONCLUSION: Taken together, our findings implicate an impact of CDKN2B-AS1 gene polymorphisms on the progression of DR.
RESUMEN
We aimed to evaluate the postoperative visual and refractive outcomes between the first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries. A retrospective cohort study was conducted and patients who had received first- and second-generation KLEx surgeries were enrolled. A total of 80 and 80 eyes were categorized into the first and second KLEx groups after exclusion, respectively. The primary outcomes were the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and safety indexes. An independent t-test and generalized estimate equation were implemented to compare the primary outcomes between the two groups. After the KLEx surgery, the UDVA showed no significant difference between the two groups throughout the study period (all p > 0.05), and the postoperative SE and safety index were also statistically identical between the two groups during the follow-up interval (all p > 0.05). There was a similar trend of visual recovery between the two groups (aOR: 0.967; 95% CI: 0.892-1.143; p = 0.844), while the amplitude of the SE change was significantly lower in the second KLEx group (aOR: 0.760; 95% CI: 0.615-0.837; p = 0.005). Nine and two unintended initial dissection of the posterior plane (UIDPP) occurred intraoperatively in the first and second KLEx groups, respectively, and the second group showed a lower risk of UIDPP (p = 0.032). In conclusion, the efficiency, predictability, and safety are similar between first- and second-generation KLEx surgeries.
RESUMEN
Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancer, remains a highly challenging cancer to treat, largely due to the late diagnosis in advanced stages of the disease, which occurs in more than half of cases [...].